Outline

A dose escalation trial (phase I/II trial) with a total dose ranging from 52.8 GyE to 73.6 GyE administered in 16 fractions over four weeks (with a single radiation dose of 3.3–4.6 GyE) was carried out on 64 lesions of 57 bone and soft tissue sarcoma patients during the period from June 1996 until February 2000. As a result, seven of the 17 patients treated with 73.6 GyE were found to have grade 3 RTOG acute reactions (skin) and dose escalation was halted at this dose level. No other grade 3 or worse acute reactions were detected. These findings made it clear that on a fractionation regimen of 16 fractions over four weeks, a total dose of 70.4 GyE was the maximum applicable dose in cases in which the skin presented a problem and a total dose of 73.6 GyE in other cases. The overall local control rate was 89% at 1 year, 63% at 3 years, and 63% at 5 years, respectively. A significant difference was found in the local control rates achieved with a total dose of 57.6 GyE or less and one of 64.0 GyE or more. The median survival time is 31 months (2–96 months) and the one-, three- and five-year survival rates are 82%, 47%, and 37%, respectively. The fixed-dose phase II trial was initiated in April 2000 and as of August 2008, 362 patients have been enrolled for treatment. The number of lesions and patients analyzed six months or longer after therapy stands at 350 lesions of 331 patients, with ten of these lesions having been treated with a dose of 73.6 GyE (4.6 GyE per fraction), 19 with 64 GyE (4.0 GyE per fraction) and 21 with 67.2 GyE (4.2 GyE per fraction). The remaining 299 lesions were treated with a dose of 70.4 GyE (4.4 GyE per fraction). As of the present, both the 2- and 5-year local control rate are 88% and 79%, and similarly the overall survival rates are 79% and 57%, respectively. Grade 3 or worse toxic reactions include two patients with acute skin toxicities (grade 3) and seven patients with late skin toxicities (grade 3: 6 patients; grade 4: 1 patient). These late skin reactions suggest that the following may be risk factors in addition to the total dose: 1) subcutaneous tumor invasion, 2) tumor volume, 3) sacrum, 4) previous surgery, 5) additional chemotherapy, and 6) irradiation from two portals. It was possible, however, to prevent these reactions by aiming for a standard dose of 70.4GyE and by modifying the irradiation method which may include irradiation from three portals, in order to reduce the dose delivered to the skin. The entire evaluable population for both the above clinical trials amounted to 414 lesions of 388 patients, and their aggregate five-year local control rate stands at 76% and their five-year overall survival rate at 54%. The 126 chordoma patients (excluding patients with the base of the skull primaries) of this total have a five-year local control rate of 89% and a five-year overall survival rate of 85%. A report on the 30 sacral chordoma patients who were observed for a period of two years or longer was published in the Clinical Cancer Research.The five-year local control rate and five-year overall survival rate for the 65 patients with osteosarcoma of the trunk were 62% and 28% and for the 63 chondrosarcoma patients 65% and 59%, respectively.